Fatal Intoxication by the Novel Cathinone 4-Fluoro-3-methyl-α-PVP.

A 30 year old non-hispanic white male was found unresponsive at his workplace and admitted to the hospital in cardiac arrest. He was pronounced deceased shortly after arrival. At autopsy the pathologist noted a 176 pound, well-nourished, atraumatic, adult male with significant bilateral frothy pulmonary edema (right lung 930 g and left lung 1,130 g), cardiomegaly (430 g), dilated ventricles and slight cerebral edema. Upon completion of the systematic toxicological analysis scope for the Franklin County Coroner's Office Toxicology Laboratory, no known drugs were found. Further review of the gas chromatography--mass spectrometry (GC--MS) full-scan library summary reports showed an unknown peak in both the blood and urine solid phase extracts. An analogue of α-pyrrolidinovalerophenone (α-PVP) was identified, and a GC--MS selected ion monitoring method was developed to identify and quantitate the presence of 4-fluoro-3-methyl-α-PVP. This method quantified the drug at 26 ng/mL in gray top femoral blood, 30 ng/mL in purple top heart blood and 20 ng/mL in red top vitreous humor. Qualitative presence was also observed in the urine but was not detected in the liver. The decedent's cause of death was determined to be due to fluoro-methyl-PVP toxicity and the manner was ruled to be accidental. Investigational follow-up interviews corroborated drug use by the deceased with a preference of research chemicals and synthetic cannabinoids via the internet. No published literature is available currently, and to the author's knowledge this is the first incident of a fatal death solely attributed to this substituted cathinone.

Broad Dataset and Methods for Counting and Localization of On-Ear Corn Kernels.

Crop monitoring and yield prediction are central to management decisions for farmers. One key task is counting the number of kernels on an ear of corn to estimate yield in a field. As ears of corn can easily have 400-900 kernels, manual counting is unrealistic; traditionally, growers have approximated the number of kernels on an ear of corn through a mixture of counting and estimation. With the success of deep learning, these human estimates can now be replaced with more accurate machine learning models, many of which are efficient enough to run on a mobile device. Although a conceptually simple task, the counting and localization of hundreds of instances in an image is challenging for many image detection algorithms which struggle when objects are small in size and large in number. We compare different detection-based frameworks, Faster R-CNN, YOLO, and density-estimation approaches for on-ear corn kernel counting and localization. In addition to the YOLOv5 model which is accurate and edge-deployable, our density-estimation approach produces high-quality results, is lightweight enough for edge deployment, and maintains its computational efficiency independent of the number of kernels in the image. Additionally, we seek to standardize and broaden this line of work through the release of a challenging dataset with high-quality, multi-class segmentation masks. This dataset firstly enables quantitative comparison of approaches within the kernel counting application space and secondly promotes further research in transfer learning and domain adaptation, large count segmentation methods, and edge deployment methods.

Corrigendum: Large-Scale Counting and Localization of Pineapple Inflorescence Through Deep Density-Estimation.

[This corrects the article DOI: 10.3389/fpls.2020.599705.].

Large-Scale Counting and Localization of Pineapple Inflorescence Through Deep Density-Estimation.

Natural flowering affects fruit development and quality, and impacts the harvest of specialty plants like pineapple. Pineapple growers use chemicals to induce flowering so that most plants within a field produce fruit of high quality that is ready to harvest at the same time. Since pineapple is hand-harvested, the ability to harvest all of the fruit of a field in a single pass is critical to reduce field losses, costs, and waste, and to maximize efficiency. Traditionally, due to high planting densities, pineapple growers have been limited to gathering crop intelligence through manual inspection around the edges of the field, giving them only a limited view of their crop's status. Through the advances in remote sensing and computer vision, we can enable the regular inspection of the field and automated inflorescence counting enabling growers to optimize their management practices. Our work uses a deep learning-based density estimation approach to count the number of flowering pineapple plants in a field with a test MAE of 11.5 and MAPD of 6.37%. Notably, the computational complexity of this method does not depend on the number of plants present and therefore efficiently scale to easily detect over a 1.6 million flowering plants in a field. We further embed this approach in an active learning framework for continual learning and model improvement.

Child Fatalities Due to Heroin/Fentanyl Exposure: What the Case History Missed.

This case report presents three unrelated children found to have heroin and/or fentanyl in their systems after general unknown systematic toxicological analysis (STA). The first case involves an 11-month-old male found unresponsive at their residence. The scene response suggested a potentially unsafe sleeping condition or a sudden unexplained infant death. The second case is a 14-month-old female found unresponsive after eating soft candies, suggesting that a choking related death may have occurred. The third case is a 12-year-old male found unresponsive in bed and foaming from the mouth. Gum was removed from the child's airway, suggesting another choking related death. The STA included a 14-drug category enzyme linked immunosorbant assay (ELISA) screening in whole blood. Cases 1 and 3 were presumptively positive for fentanyl, while Case 2 was presumptively positive for opiates and fentanyl. Reflex confirmation was performed in blood, urine and gastric contents, by solid-phase extraction (SPE) for 12 opiates including morphine and 6-monoacetylmorphine (6MAM) by gas chromatography-mass spectrometry (GC-MS) and for fentanyl, norfentanyl, and novel analogs, by liquid chromatography tandem mass spectrometry (LC-MS-MS). High concentrations of fentanyl and 6MAM in the gastric contents of Case 1, along with the presence of diacetylmorphine, suggested probable enteral ingestion of heroin and fentanyl, separately or in a combined formulation. Interpretation of the toxicology results could not determine a probable route of exposure to heroin/fentanyl in Case 2, however, the cause of death was clearly related to this drug mixture. In Case 3, the presence of acetylfentanyl suggested an illicit fentanyl exposure. The intention of this case report is to demonstrate the need for a STA approach for all non-trauma postmortem cases regardless of case circumstances, age or suspicion of drug use.

Decoupling kinematics and mechanics reveals coding properties of trigeminal ganglion neurons in the rat vibrissal system.

Tactile information available to the rat vibrissal system begins as external forces that cause whisker deformations, which in turn excite mechanoreceptors in the follicle. Despite the fundamental mechanical origin of tactile information, primary sensory neurons in the trigeminal ganglion (Vg) have often been described as encoding the kinematics (geometry) of object contact. Here we aimed to determine the extent to which Vg neurons encode the kinematics vs. mechanics of contact. We used models of whisker bending to quantify mechanical signals (forces and moments) at the whisker base while simultaneously monitoring whisker kinematics and recording single Vg units in both anesthetized rats and awake, body restrained rats. We employed a novel manual stimulation technique to deflect whiskers in a way that decouples kinematics from mechanics, and used Generalized Linear Models (GLMs) to show that Vg neurons more directly encode mechanical signals when the whisker is deflected in this decoupled stimulus space.

Evidence for Functional Groupings of Vibrissae across the Rodent Mystacial Pad.

During natural exploration, rats exhibit two particularly conspicuous vibrissal-mediated behaviors: they follow along walls, and "dab" their snouts on the ground at frequencies related to the whisking cycle. In general, the walls and ground may be located at any distance from, and at any orientation relative to, the rat's head, which raises the question of how the rat might determine the position and orientation of these surfaces. Previous studies have compellingly demonstrated that rats can accurately determine the horizontal angle at which a vibrissa first touches an object, and we therefore asked whether this parameter could provide the rat with information about the pitch, distance, and yaw of a surface relative to its head. We used a three-dimensional model of the whisker array to construct mappings between the horizontal angle of contact of each vibrissa and every possible (pitch, distance, and yaw) configuration of the head relative to a flat surface. The mappings revealed striking differences in the patterns of contact for vibrissae in different regions of the array. The exterior (A, D, E) rows provide information about the relative pitch of the surface regardless of distance. The interior (B, C) rows provide distance cues regardless of head pitch. Yaw is linearly correlated with the difference between the number of right and left whiskers touching the surface. Compared to the long reaches that whiskers can make to the side and below the rat, the reachable distance in front of the rat's nose is relatively small. We confirmed key predictions of these functional groupings in a behavioral experiment that monitored the contact patterns that the vibrissae made with a flat vertical surface. These results suggest that vibrissae in different regions of the array are not interchangeable sensors, but rather functionally grouped to acquire particular types of information about the environment.

Probability distributions of whisker-surface contact: quantifying elements of the rat vibrissotactile natural scene.

Analysis of natural scene statistics has been a powerful approach for understanding neural coding in the auditory and visual systems. In the field of somatosensation, it has been more challenging to quantify the natural tactile scene, in part because somatosensory signals are so tightly linked to the animal's movements. The present work takes a step towards quantifying the natural tactile scene for the rat vibrissal system by simulating rat whisking motions to systematically investigate the probabilities of whisker-object contact in naturalistic environments. The simulations permit an exhaustive search through the complete space of possible contact patterns, thereby allowing for the characterization of the patterns that would most likely occur during long sequences of natural exploratory behavior. We specifically quantified the probabilities of 'concomitant contact', that is, given that a particular whisker makes contact with a surface during a whisk, what is the probability that each of the other whiskers will also make contact with the surface during that whisk? Probabilities of concomitant contact were quantified in simulations that assumed increasingly naturalistic conditions: first, the space of all possible head poses; second, the space of behaviorally preferred head poses as measured experimentally; and third, common head poses in environments such as cages and burrows. As environments became more naturalistic, the probability distributions shifted from exhibiting a 'row-wise' structure to a more diagonal structure. Results also reveal that the rat appears to use motor strategies (e.g. head pitches) that generate contact patterns that are particularly well suited to extract information in the presence of uncertainty.

Spatiotemporal Patterns of Contact Across the Rat Vibrissal Array During Exploratory Behavior.

The rat vibrissal system is an important model for the study of somatosensation, but the small size and rapid speed of the vibrissae have precluded measuring precise vibrissal-object contact sequences during behavior. We used a laser light sheet to quantify, with 1 ms resolution, the spatiotemporal structure of whisker-surface contact as five naïve rats freely explored a flat, vertical glass wall. Consistent with previous work, we show that the whisk cycle cannot be uniquely defined because different whiskers often move asynchronously, but that quasi-periodic (~8 Hz) variations in head velocity represent a distinct temporal feature on which to lock analysis. Around times of minimum head velocity, whiskers protract to make contact with the surface, and then sustain contact with the surface for extended durations (~25-60 ms) before detaching. This behavior results in discrete temporal windows in which large numbers of whiskers are in contact with the surface. These "sustained collective contact intervals" (SCCIs) were observed on 100% of whisks for all five rats. The overall spatiotemporal structure of the SCCIs can be qualitatively predicted based on information about head pose and the average whisk cycle. In contrast, precise sequences of whisker-surface contact depend on detailed head and whisker kinematics. Sequences of vibrissal contact were highly variable, equally likely to propagate in all directions across the array. Somewhat more structure was found when sequences of contacts were examined on a row-wise basis. In striking contrast to the high variability associated with contact sequences, a consistent feature of each SCCI was that the contact locations of the whiskers on the glass converged and moved more slowly on the sheet. Together, these findings lead us to propose that the rat uses a strategy of "windowed sampling" to extract an object's spatial features: specifically, the rat spatially integrates quasi-static mechanical signals across whiskers during the period of sustained contact, resembling an "enclosing" haptic procedure.

Influenza immunization in Canada's low-income population.

BACKGROUND: Immunization offers the best protection from influenza infection. Little evidence describes disparities in immunization uptake among low-income individuals. Higher rates of chronic disease put this population at increased risk of influenza-related complications. This analysis examines if the type of main source of household income in low-income groups affects influenza immunization uptake. We hypothesized that individuals on social assistance have less access to immunization compared to those with employment earnings or seniors' benefits. METHODS: Data was obtained from the Canadian Community Health Survey annual component 2009-2010. A total of 10,373 low-income respondents (<20,000$ Canadian per annum) were included. Logistic regression, stratified according to type of provincial publicly funded immunization program, was used to examine the association between influenza immunization (in the last 12 months) and main source of household income (employment earnings; social assistance as a combination of employment insurance or worker's compensation or welfare; or seniors' benefits). RESULTS: Overall, 32.5% of respondents reported receiving influenza immunization. In multivariable analysis of universal publicly funded influenza immunization programs, those reporting social assistance (AOR 1.24, 95% CI 1.02-1.51) or seniors' benefits (AOR 1.56, 95% CI 1.23-1.98) were more likely to be immunized compared to those reporting employment earnings. Similar results were observed for high-risk programs. CONCLUSIONS: Among the low-income sample, overall influenza immunization coverage is low. Those receiving social assistance or seniors' benefits may have been targeted due to higher rates of chronic disease. Programs reaching the workforce may be important to attain broader coverage. However, CCHS data was collected during the H1N1 pandemic influenza, thus results may not be generalizable to influenza immunization in non-pandemic years.

Hybrid cognitive behavioral therapy versus relaxation training for co-occurring anxiety and alcohol disorder: a randomized clinical trial.

OBJECTIVE: Treatment for alcohol use disorder (AUD) is far less effective for those with a co-occurring anxiety disorder. Surprisingly, adding an independent anxiety treatment to AUD treatment does not substantially improve the poor alcohol outcomes of these patients. This may reflect the lack of attention from independent treatments to the dynamic interaction of anxiety symptoms with alcohol use and drinking motivation. On the basis of this view, we assembled a cognitive behavioral therapy (CBT) program designed to both reduce anxiety symptoms and weaken the links between the experience of anxiety and the motivation to drink. METHOD: 344 patients undergoing residential AUD treatment with current social phobia, generalized anxiety disorder, or panic disorder were randomly assigned to receive either the CBT or an active comparison treatment, progressive muscle relaxation training (PMRT). Assessments took place immediately following treatment and 4 months later (n = 247). RESULTS: As predicted, the CBT group demonstrated significantly better alcohol outcomes 4 months following treatment than did the PMRT group. Although both groups experienced a substantial degree of anxiety reduction following treatment, there were no significant group differences immediately after treatment and only a slight advantage for the CBT group 4 months after treatment. CONCLUSIONS: These findings suggest that specific interventions aimed at weakening the association between the experience of anxiety and drinking motivation play an important role in improving the alcohol outcomes of these difficult-to-treat patients beyond that of anxiety reduction alone.

ENSO drove 2500-year collapse of eastern Pacific coral reefs.

Cores of coral reef frameworks along an upwelling gradient in Panamá show that reef ecosystems in the tropical eastern Pacific collapsed for 2500 years, representing as much as 40% of their history, beginning about 4000 years ago. The principal cause of this millennial-scale hiatus in reef growth was increased variability of the El Niño-Southern Oscillation (ENSO) and its coupling with the Intertropical Convergence Zone. The hiatus was a Pacific-wide phenomenon with an underlying climatology similar to probable scenarios for the next century. Global climate change is probably driving eastern Pacific reefs toward another regional collapse.

Emergency department management of undifferentiated abdominal pain with hyoscine butylbromide and paracetamol: a randomised control trial.

OBJECTIVE: To compare the effectiveness of paracetamol, hyoscine butylbromide and the combination of paracetamol plus hyoscine butylbromide (paracetamol + hyoscine butylbromide) in the management of patients with acute undifferentiated abdominal pain attending the emergency department (ED). SETTING: A large teaching hospital with an annual ED census of 120,000 adult patients. METHODS: A prospective, randomised placebo controlled trial of a convenience sample of patients attending the ED. The trial compared the analgesic effect of intravenous hyoscine butylbromide, oral paracetamol and the combination of both drugs using a Visual Analogue Scale pain scoring tool. Rescue analgesia was administered when pain was inadequately controlled by trial medication. RESULTS: 132 patients were recruited to the trial. At 30 min, all analgesic combinations produced significant similar levels of pain relief. At 60 min after administration of the trial medication, mean reductions in pain scores for patients receiving paracetamol only were significantly greater than those receiving paracetamol + hyoscine butylbromide (ANCOVA model, p=0.0180). No relationship was seen between treatment arm and the need for rescue analgesia (χ(2), p value=0.846). CONCLUSION: The trial data suggest that oral paracetamol is at least as effective as intravenous hyoscine butylbromide and a combination of both drugs in the management of acute undifferentiated abdominal pain presenting to the ED. Based on these results and factors such as cost and tolerability, we recommend single agent paracetamol as the agent of choice for the management of acute mild to moderate undifferentiated abdominal pain. TRIAL REGISTRATION NUMBER: MHRA Ref: 19717/0226/001-0001; European Clinical Trials Database. EUDRAct No: 2006-005395-40.

Meta-analysis of supplemental treatment for depressive and anxiety disorders in patients being treated for alcohol dependence.

Approximately half of those receiving treatment for an alcohol use disorder (AUD) also suffer with an anxiety or depressive (internalizing) disorder. Because all internalizing disorders mark a poor alcohol treatment outcome, it seems reasonable to supplement AUD treatment with a psychiatric intervention when these disorders co-occur with AUD. However, this conclusion may be faulty given that the various possible interrelationships between AUD and internalizing disorders do not uniformly imply a high therapeutic yield from this approach. Unfortunately, the studies conducted to date have been too few and too small to resolve this important clinical issue with confidence. Therefore, we used a meta-analytic method to synthesize the effects from published randomized controlled trials examining the impact of supplementing AUD treatment with a psychiatric treatment for co-occurring internalizing disorder (N = 15). We found a pooled effect size (d) of .32 for internalizing outcomes and .22 for a composite of alcohol outcomes; however, the alcohol outcomes effect sizes were greater than this for some specific outcome domains. Subgroups that differed in terms of internalizing outcomes included treatment type (medication vs. cognitive behavioral therapy) and treatment focus (anxiety vs. depression). There was also a trend for the studies with better internalizing disorder outcomes to have better alcohol outcomes. These results indicate that clinical outcomes (both psychiatric and alcohol-related) could be somewhat improved by supplementing AUD treatment with psychiatric treatment for co-occurring internalizing disorder.

Political dreams, practical boundaries: the case of the Nursing Minimum Data Set, 1983-1990.

The initial development of the Nursing Minimum Data Set (NMDS) was analyzed based on archival material from Harriet Werley and Norma Lang, two nurses involved with the project, and American Nurses Association materials. The process of identifying information to be included in the NMDS was contentious. Individual nurses argued on behalf of particular data because of a strong belief in how nursing practice (through information collection) should be structured. Little attention was paid to existing practice conditions that would ultimately determine whether the NMDS would be used.

Defining nursing practice: the ANA Social Policy Statement, 1980-1983.

This article examines the initial development of the American Nurses Association's Social Policy Statement (SPS). The methodology used is the Social History of Technology. This approach provided the means to treat the SPS as an information practice or tool that resides within a technological system composed of skills, tools, and knowledge. The data for analysis include archive material and secondary sources. This study concludes that development of the SPS was inherently a local exercise in prioritizing, organizing, and promoting certain skills, tools, and knowledge associated with nursing practice, an exercise that integrated contextual influences with local realities. The study also provides a means to reflect on the development of contemporary information practices.

A dimensional analysis of patient-centered care.

BACKGROUND: Patient-centered care (PCC) is a poorly conceptualized phenomenon and can indicate anything from soothing room design, emotional support of patients, customization of meals, to support of patient decision making. This inconsistency across the clinical and research literature makes the application of PCC difficult. OBJECTIVES: The objective of this study was to identify dimensions of PCC as found in the literature. METHODS: A dimensional analysis of PCC was conducted from 69 clinical and research articles published from 2000 to 2006. Coding of the literature for the perspective, context, conditions, process, and consequences of PCC was completed. These codes were used to determine literature selected for inclusion, organize article content, and frame the delineation of PCC. RESULTS: Alleviating vulnerabilities, consisting of both compromised physiological states and threats to individual identity, was constant throughout the literature. Therapeutic engagement was the process sustaining the patient during an illness episode that necessitated service use and involved allocating time, carrying out information practices, knowing the patient, and developing a relationship. This process occurs during nurse-patient interaction, sustained during successive interactions, and reinforced by the information practices of a particular setting. DISCUSSION: The interaction between nurse and patient is central to the effective study and application of PCC. Appropriate use of PCC can improve study outcomes and measurements by clarifying the variables involved, and PCC holds great promise to frame patient outcome and satisfaction research by analyzing how and with what effect nurses alleviate patient vulnerability. Moreover, consideration of information practices as a critical supporting structure of nurse-patient interaction can be explored.

Role of alternatively spliced tissue factor in pancreatic cancer growth and angiogenesis.

Increased tissue factor (TF) expression is observed in many types of cancer, associated with more aggressive disease, and in thrombosis. The mechanism by which TF promotes tumor growth remains unclear. Anticoagulation has been shown to result in a trend toward improved survival; no direct antitumor effect has been shown in cancer patients. Alternatively spliced tissue factor (asTF) was recently described, in which exon 5 is deleted. Because of a frame-shift in exon 6, the transmembrane and cytoplasmic domains are replaced with a unique COOH-terminal domain, making asTF soluble. Both alternatively spliced human tissue factor (asHTF) and full-length tissue factor (flTF) are expressed in human pancreatic cancer lines and in pancreatic cancer specimens. We studied the role of asHTF and flTF in a mouse model of pancreatic cancer. Although lacking procoagulant activity, asTF promotes primary growth of human pancreatic cancer cells in mice and augments tumor-associated angiogenesis. This body of work suggests a new paradigm for the role of TF in pancreatic cancer: that asHTF contributes to cancer growth, independent of procoagulant activity.

The Department of Veterans Affairs pre- and post-doctoral nurse fellowships: diverse opportunities for research.

The purpose of this article is to explicate research funding and training opportunities available through the Department of Veterans Affairs to nurses seeking advanced preparation at the pre- and post-doctoral levels. A brief discussion of the available resources including student stipend and health insurance, workspace, and research support is presented. Additionally, articulation of the benefits and challenges associated with these types of fellowships is delineated from the perspective of a fellow, Department of Veterans Affairs (VA) site preceptor, and dissertation faculty. Discussion of the post-doctoral fellowship and the extensive resources of the VA related to overall research career development are also addressed.

Alternatively spliced human tissue factor promotes tumor growth and angiogenesis in a pancreatic cancer tumor model.

INTRODUCTION: Tissue Factor (TF) expression is observed in many types of cancer, associated with more aggressive disease, and thrombosis. Alternatively-spliced human tissue factor (asHTF) has recently been identified in which exon 5 is deleted. asHTF is soluble due to the substitution of the transmembrane and cytoplasmic domains of exon 6 with a unique COOH-terminal domain. MATERIALS AND METHODS: We examine the expression and function of asHTF and full-length Tissue Factor ((FL)TF) in six human pancreatic cancer cells. Further, we transfected asHTF, (FL)TF, and control expression vectors into a non-expressing, human pancreatic cancer line (MiaPaCa-2). We studied the procoagulant activity of asHTF and (FL)TF and the effect on tumor growth in mice. RESULTS: asHTF is expressed in 5 of 6 human pancreatic cancer cell lines, but not in normal human fibroblasts, nor the MiaPaCa-2 line. (FL)TF conferred procoagulant activity, but asHTF did not. Transfected cells were injected subcutaneously in athymic mice. Interestingly, compared with control transfection, (FL)TF expression was associated with reduced tumor growth (mean 7 mg vs 85 mg), while asHTF-expression was associated with enhanced tumor growth (mean 389 mg vs. 85 mg). asHTF expression resulted in increased mitotic index and microvascular density. CONCLUSIONS: These data suggests that asHTF expression promotes tumor growth, and is associated with increased tumor cell proliferation and angiogenesis in vivo. Our results raise a new perspective on the understanding of the relationship between TF expression and cancer growth, by showing a dissociation of the procoagulant activity of (FL)TF and the cancer-promoting activity of asHTF.